title: The structure of neuronal calcium sensor-1 in solution revealed by molecular dynamics simulations.
abstract: Neuronal calcium sensor-1 (NCS-1) is a protein able to trigger signal transduction processes by binding a large number of substrates and re-shaping its structure depending on the environmental conditions. The X-ray crystal structure of the unmyristoilated NCS-1 shows a large solvent-exposed hydrophobic crevice (HC); this HC is partially occupied by the C-terminal tail and thus elusive to the surrounding solvent. We studied the native state of NCS-1 by performing room temperature molecular dynamics (MD) simulations starting from the crystal and the solution structures. We observe relaxation to a state independent of the initial structure, in which the C-terminal tail occupies the HC. We suggest that the C-terminal tail shields the HC binding pocket and modulates the affinity of NCS-1 for its natural targets. By analyzing the topology and nature of the inter-residue potential energy, we provide a compelling description of the interaction network that determines the three-dimensional organization of NCS-1.
authors.affiliation: Center S3, CNR Institute Nanoscience, Modena, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Bellucci
authors.forename: Stefano
authors.initials: S
authors.lastname: Corni
authors.forename: Rosa
authors.initials: R
authors.lastname: Di Felice
authors.forename: Emanuele
authors.initials: E
authors.lastname: Paci
mesh_terms: D016000:Cluster Analysis; D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D051580:Neuronal Calcium-Sensor Proteins / Q000737:chemistry*; D009479:Neuropeptides / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; C101464:frequenin calcium sensor proteins